The incidence of esophageal adenocarcinoma has been rising rapidly over the past two decades for unclear reasons. The most important risk factor for this cancer is Barrett's esophagus, a condition resulting from the reflux of gastric contents into the esophagus. In Barrett's esophagus the normal squamous cell lining of the esophagus is replaced by a specialized cell lining containing intestinal features. Risk factors associated with the development of Barrett's esophagus are not well defined. We now propose to combine the resources of two large, ongoing prospective cohort studies, the Nurses'Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), in which information on potential risk factors for Barrett's esophagus were collected at baseline and repeatedly updated over time. Cohort participants who have undergone upper endoscopy will form the basis of a nested cohort study comparing those with and without histologically- documented Barrett's esophagus. In order to conduct meaningful epidemiologic studies of risk factors for Barrett's esophagus among the participants of the NHS and HPFS, we must validate each case by review of pathologic records. We have already verified histologically-[sic] documented cases of Barrett's esophagus within the NHS. The currently proposed project would verify cases of Barrett's esophagus within the HPFS and permit pooling of data from these cohorts. Because the NHS participants are women and the HPFS participants are men, we will be able to detect gender-related differences in risk factors for Barrett's esophagus. The proposed project will begin these pooled analyses by studying how body fat distribution and cigarette smoking are related to Barrett's esophagus in both men and women. PROJECT NARRATIVE: RELEVANCE The goals of the project are to better understand reasons why people develop Barrett's esophagus, a condition that can lead to esophageal adenocarcinoma (a type of cancer whose frequency is rising faster than most other cancers). One of the aims of this proposed project addresses the suspected association between obesity and Barrett's esophagus, especially relevant during our nation's current obesity epidemic.